Growth factor and cytokine regulation of chondroitin sulfate proteoglycans by astrocytes
Article first published online: 20 JUN 2005
Copyright © 2005 Wiley-Liss, Inc.
Volume 52, Issue 3, pages 209–218, 15 November 2005
How to Cite
Smith, G. M. and Strunz, C. (2005), Growth factor and cytokine regulation of chondroitin sulfate proteoglycans by astrocytes. Glia, 52: 209–218. doi: 10.1002/glia.20236
- Issue published online: 29 SEP 2005
- Article first published online: 20 JUN 2005
- Manuscript Accepted: 4 APR 2005
- Manuscript Received: 26 JUL 2004
- NIH/NINDS. Grant Numbers: NS33776, NS38126 KSCHIRT 2:16
- chondroitin sulfate proteoglycan;
- transforming growth factor-β1;
- epidermal growth factor;
- wound healing
After injury to the adult central nervous system (CNS), numerous cytokines and growth factors are released that contribute to reactive gliosis and extracellular matrix production. In vitro examination of these cytokines revealed that the presence of transforming growth factor-β1 (TGF-β1) and epidermal growth factor (EGF) greatly increased the production of several chondroitin sulfate proteoglycans (CSPG) by astrocytes. Treatment of astrocytes with other EGF-receptor (ErbB1) ligands, such as TGF-α and HB-EGF, produced increases in CSPG production similar to those observed with EGF. Treatment of astrocytes, however, with heregulin, which signals through other members of the EGF-receptor family (ErbB2, ErbB3, ErbB4), did not induce CSPG upregulation. The specificity of activation through the ErbB1 receptor was further verified by using a selective antagonist (AG1478) to this tyrosine kinase receptor. Western blot analysis of astrocyte supernatant pre-digested with chondroitinase ABC indicated the presence of multiple core proteins containing 4-sulfated or 6-sulfated chondroitin. To identify some of these CSPGs, Western blots were screened using antibodies to several known CSPG core proteins. These analyses showed that treatment of astrocytes with EGF increased phosphacan expression, whereas treatment with TGF-β1 increased neurocan expression. Reverse transcription-polymerase chain reaction (RT-PCR) was used to examine the expression of these molecules in vivo, which result in increased expression of TGF-β1, EGF-receptor, neurocan, and phosphacan after injury to the brain. These data begin to elucidate some of the injury-induced growth factors that regulate the expression of CSPGs which could be targeted in the future to modulate CSPG production after injury to the central nervous system. © 2005 Wiley-Liss, Inc.